Transkript

1 Mode of action based risk assessment of chemical ingredients in cosmetics: What can Swedish toxicological sciences contribute in the future? Ian A Cotgreave Swedish toxicology scinces research center Karolinska Institute Gärtuna

2 2 Format for the lecture The ban on use of animals in risk assessment of cosmetics ingredients: Cause and effects. Responses to the ban in contemporary scientific efforts. From pathology to pathways in the New Toxicology Examples of current international scientific colaborations IMI, Tox21/ToxCast, human toxome etc Integrated testing strategies, what are they? EPAA SEURAT-1 From tool box, through AOPs to PoCs in safety assessment Examples of coming investments in the EU Swedish commitments to developments in the area VR-M3R, 3R Centre of Excellence Swetox: A potential rallying point for Swedish research into alternatives via the 3Ms and 3Rs? Tool box developments, AOPs and validation of test methods, PoCs in risk assessment and risk mitigation So how can we all help in Sweden. Ideas???

3 MARCH 2013: THE EU INTRODUCES A TOTAL BAN ON THE USE OF EXPERIMENTALANIMALS IN SAFETY TESTING OF ALL CHEMICAL INGREDIENTS IN ALL COSMETIC PRODUCTS TO BE SOLD WITHIN THE EU

13 But the EU is spear-heading the development of integrated testing strategies, using efforts from all stake holders EU INTEGRATED TESTING STRATEGIES (ITS) EU-EFPIA EUROPEAN PARTNERSHIP FOR ALTERNATIVES TO ANMIALS EPPA FP7-COSMETICS EUROPE SEURAT-1

14 So what is an ITS and how do the regulatory authorities see them?

15

16

17

18

19

20

21

22 EPAA-ITS (2006-) Within the EPAA, we understand ITS as a way of working based on panels of complementary approaches that enable effectively linking different (non-animal) methods in such a way that the combined and reproducible results suffice for appropriate risk assessment/safety assessment of chemical substances or products. ITS can integrate non-animal and animal testing elements as well as non-testing, i.e. computer based methods. We are intimately convinced that such approaches have a concomitant impact on the 3Rs 4/14/2014

23 ITS is a way of working, applied commonly within industry, combining the use of different testing and non-testing methods in an optimal manner for decision making purposes. Within the perspective of the 3Rs, its main goals are to: Improve efficiency, effectiveness and quality of hazard and risk assessment Decrease costs Contribute to the 3Rs while ensuring a sufficient protection of human health and the environment Although regulatory schemes allow for the Implementation of ITS, regulatory acceptance of data generated under ITS needs further improvement

24 SEURAT-1!! (2011-) To define a new mode of action paradigm in human risk assessment based on animal-free, repeated exposure toxicity predictions.

25 Georges-Pierre Seurat

26 Background Legislation: The EU "Cosmetics Directive" foresees a deadline in 2013 for animal testing of cosmetic products in the fields of repeated dose toxicity, reproductive toxicity and toxicokinetics To overcome the lack of scientific knowledge for implementation of alternative testing solutions the Health Programme of DG Research and Innovation defined a longterm target: Safety Evaluation Ultimately Replacing Animal Testing (SEURAT) which will have an impact on many different areas including drug development, industrial chemicals, biocides etc

27 First step: Seurat-1 Research Initiative Towards the replacement of in vivo repeated dose systemic toxicity testing Joint funding by the European Commission and a specific industrial sector (cosmetics industry / Colipa) 25 million EC & 25 million Cosmetics Europe OBJECTIVES Development of an innovative concept for repeated dose systemic toxicity testing. Proof of concept for a future full implementation of a modeof-action strategy. Development of innovative testing methods more predictive than existing testing procedures. ~ 70 research groups from European Universities, Public Research Institutes and Companies (more than 30% SMEs)

28 28 SEURAT-1 objectives Development of an innovative concept for repeated dose systemic toxicity testing. Proof of concept for a future full implementation of a mode-of-action strategy. Development of innovative testing methods more predictive than existing testing procedures.

30 The Strategy of SEURAT-1 Biokinetic modelling to extrapolate between in vitro test concentrations and repeated dose organ exposure in vivo. Computational toxicology to associate chemicals with molecular initiating events and describe metabolism. Use of high content analysis tools including `omics to describe modes-of-action at the molecular level. Systems biology approaches to model modes-of-action dynamics at the molecular scale for quantitative analysis. Proof-of-concept exercise to demonstrate a mode-of-action based integrated test system to predict sub-chronic liver toxicity. Feasibility study to show how test data can be used in a safety assessment context.

31 The 7 Building Blocks of SEURAT-1 Call «FP7-health-2010 Alternative Testing» Projects SEP COACH (secretariat) Towards the replacement of in vivo repeated dose systemic toxicity testing ~ 70 research groups from European Universities, Public Research Institutes and Companies (more than 30% SMEs)

39 SEURAT-1 is now desiging high level PoC study on read-across at the top of the pyramid Categories CAS # Category # Chemical Name Methyl parathion Group 6-ok Parathion Chemical similarity plausible for read across aassessment? Presence in filtered spreadsheet*? No longer in large spreadsheet once filtered*. No longer in large spreadsheet once filtered*. Availability/Suitability of endpoint data for Seurat-1 purposes** (refer to GRASP spreadsheets)? Suitability of test articles for in vitro assays? Availability of high content information? (cite sources) Background for short listing Fenitrothion Trifluralin Group 7-ok Benfluralin Paired with 4- nitrotoluene, 3- nitrotoluene and 2,4- dinitrotoluene in filtered spreadhseet Included in filtered spreadsheet* Included in filtered spreadsheet* COMPOUNDS ARE BEING GROUPED FOR TESTING IN BEST PRACICE AOPS IN BEST PRCATICE SYSTEMS QUANTITATIVE DATA SOUGHT, FOCUS ON POINT OF DEPARTURE FROM SAFETY

40 Looking forward, what is devloping, and how can we all get involved in Sweden?

44 So what is happening i Sweden? Can we contribute? VR M3R RESEARCH FUNDING PROGRAM (CIRCA 5-7 MKR PER ANNUM) SPECIFIC CALLS WITH FORMAS? OTHER GRANT FUNDING BODIES? A CENTER OF EXCELLENCE FOR 3RS? (JÖNKÖPING!)

Swedish Chapter of International Society of Indoor Air Quality and Climate Aneta Wierzbicka Swedish Chapter of International Society of Indoor Air Quality and Climate Independent and non-profit Swedish

Thesis for the degree of Licentiate of Philosophy, Östersund 2014 Understanding Innovation as an Approach to Increasing Customer Value in the Context of the Public Sector Klas Palm Supervisors: Håkan Wiklund

THERE ARE SO MANY REASONS FOR WORKING WITH THE ENVIRONMENT! It s obviously important that all industries do what they can to contribute to environmental efforts. The MER project provides us with a unique

UMEÅ UNIVERSITY Faculty of Medicine Spring 2012 EVALUATION OF ADVANCED BIOSTATISTICS COURSE, part I 1) Name of the course: Logistic regression 2) What is your postgraduate subject? Tidig reumatoid artrit

The reception Unit Adjunkten - for newly arrived pupils Shortly on our work Number of received pupils: - 300 for school year 2014-2015 - 600 for school year 2015-2016 - 220 pupils aug-dec 2016 - ca. 45

Presentation 2010-09-30 The road to Recovery in a difficult Environment - a presentation at the Workability International Conference Social Enterprises Leading Recovery in Local and Global Markets in Dublin

Innovation Enabled by ICT A proposal for a Vinnova national Strategic innovation Program Ulf Wahlberg, VP INdustry and Research Relations Ericsson AB Ericsson AB 2012 April 2013 Page 1 Five technological

1. Basic information 1.1. Name of the Artist-in-Residence centre 0/100 1.2. Name of the Residency Programme (if any) 0/100 1.3. Give a short description in English of the activities that the support is

Swedish Science Policy conference KVA 2011-04-06 Tuula Teeri A reassessment of the role of universities in Europe and throughout the World Economic development based on expertise, environmental change,

Strategic Research Areas Modelling: on-going (includes modelling and characterisation) Manufacturing Development Potential new area in future Materials development Potential new area in future Strategic

Name: Year 9 w. 4-7 The leading comic book publisher, Marvel Comics, is starting a new comic, which it hopes will become as popular as its classics Spiderman, Superman and The Incredible Hulk. Your job

ASSESSMENT AND REMEDIATION FOR CHILDREN WITH SPECIAL EDUCATIONAL NEEDS: THE ROLE OF WORKING MEMORY, COMPLEX EXECUTIVE FUNCTION AND METACOGNITIVE STRATEGY TRAINING Avdelningen för psykologi Mittuniversitetet

1(7) School of Management and Economics Course syllabus Course Code FEN305 Reg.No. EHVc 2005:6 Date of decision 2004-12-22 Course title in Swedish Course title in English Language of instruction Subject

Cross sectional planning for pandemic influenza in Sweden The task 1. Integrated planning across different sectors. A pandemic will impact on the whole of government and society. While Norway has a well-developed

Evaluation Ny Nordisk Mat II Appendix 1. Questionnaire evaluation Ny Nordisk Mat II English version A. About the Program in General We will now ask some questions about your relationship to the program

Demonstration driver English Svenska Beijer Electronics AB 2000, MA00336A, 2000-12 Beijer Electronics AB reserves the right to change information in this manual without prior notice. All examples in this

SICS Introducing Internet of Things in Business Christer Norström, CEO SICS In collaboration with Lars Cederblad at Level21 AB A NOT CONNECTED PRODUCT TO A CONNECTED PRODUCT IOT introduction Examples What